The purpose of these studies is to establish the basic developmental and cellular events operating in regulating the genes for fetal (gamma) and adult (beta A and beta C) globin synthesized by sheep erythroid cells. We have found that beta C globin synthesis may be induced by erythropoietin (epo) in erythroid stem cells from all gestational ages beyond 50 days at the expense of either fetal, or late in gestation, beta A globin synthesis. Those colonies derived from primative stem cells make proportionally more beta C globin than do colonies derived from late stem cells. In contrast, in animals lacking the beta C globin gene, epo concentration appears to have no role in modulating the proportion of gamma and beta globin synthesis in erythroid colonies in vitro. Furthermore, acute anemia and epo injection in young lambs fails to induce gamma globin synthesis. The ratios and beta C and beta A globin synthesis during erythroid maturation appear to be stable in vivo but we found that the fraction of beta C globin synthesis in mature colonies was greater than that found in primative colonies. Thymectomy at 60-80 days resulted in the expected lymphopenia at birth but had no effect on the pattern of hemoglobin switching during the perinatal period.